Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This phase II study was designed to assess the therapeutic potential of intensive course treatment with three anticancer agents: 50 mg of cisplatin on day 1, 40 mg/m2 of epirubicin on day 2, and 250 mg of 5-fluorouracil on days 2 through 5. Drug courses were repeated every 2 weeks and most patients received between 4 and 6 courses. Thirty-five patients with measurable advanced solid cancers entered the study. They consisted of 16 gastric, 5 colorectal, 4 gallbladder, 3 pancreatic, 3 lung, 2 esophageal, 1 uterine, and 1 ovarian cancers. Of the 35 patients, 29 were evaluated for therapeutic effect of the regimen, and the overall response rate was 31.0% (5 CR + 4 PR/29). A 33.3% rate of tumor regression, consisting of 2 complete responses (CR) and 3 partial responses (PR) out of 15 patients (2 CR + 3 PR/15), was seen for gastric cancers. For the other types of tumors the responses were achieved in 2 lung cancers (1 CR + 1 PR/3). 1 uterine cancer (1 CR/1), and 1 ovarian cancer (1 CR/1). The esophageal, colorectal, pancreatic, and gallbladder cancers were unresponsive to this regimen. Toxicities of the drug treatment were clinically tolerable and consisted of general malaise, nausea, vomiting, stomatitis, alopecia, and leucopenia. However, two patients died of uncontrollable metabolic acidosis after 1 and 2 courses, respectively. This intensive course treatment appears to promote the regression of gastric, lung, and gynecologic cancers.
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PMID:A phase II study of 5-fluorouracil, cisplatin, and 4'-epirubicin in the treatment of advanced solid cancers. 845 15

Forty-two patients affected by either stage III and IV ovarian cancer with residual tumor after surgery or recurrent ovarian cancer entered a phase II study of the combination carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2 every 28 days. Thirty-eight patients were evaluable for response and of these 27 obtained complete or partial remission with a 71% overall remission (clinical complete remission 45%; partial remission 26%). Treatment tolerability was on the whole good. The most frequent side effects were leukopenia (76%), anemia (67%) and nausea/vomiting (60%). Thrombocytopenia was present in 31% of the patients, but nearly always to a mild degree except for one grade 4 case. No other grade 4 side effect was observed. We did not observe any cases of nephrotoxicity and only two patients complained of paresthesia. This carboplatin-cyclophosphamide combination in advanced ovarian carcinoma produces comparable results, in terms of objective responses, to those obtained with standard cisplatin-based regimens, with suggestion of a better toxicological profile.
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PMID:A phase II study of carboplatin and cyclophosphamide in advanced ovarian carcinoma. 845 65

Sixty-six patients with ovarian cancer were treated with low-dose consecutive CP (LDC-CP) consisting of cyclophosphamide (CPM: 500 mg/m2, day 1) and CDDP (10 mg/m2, days 1-7). Two-9 (median: 4) courses of LDC-CP were given following reduction surgery (42 cases) or preceding primary debulking (24 cases). Among 66 cases, 12 with stage Ic were not evaluable (NE). The response rate (CR + PR/evaluable) for stages II-IV was 57.4% (12 + 19/54). Histologically, serous and endometrioid type showed a significantly (p < 0.001) higher response rate (77.5% among 40 evaluable) compared to the other histologic type (0% among 14). Toxicities including nausea/vomiting and renal impairment were markedly mild or almost absent despite the lack of any particular care. Grade 3 leucopenia and thrombocytopenia were observed only in 4.2%, and 2.5% of total 284 courses, respectively. Mean survival time by stage was 1,309 days for stage I, 809 days for stage II, 1,180 days for stage III, and 691 days for stage IV, with a significant difference among stages (p = 0.0452). In stages III and IV disease, significant prognostic factors included 1) response to chemotherapy, 2) no. of LDC-CP courses, 3) histologic subtype, 4) performance status, and 5) tumor size. Thus, LDC-CP is considered to be a useful chemotherapeutic regimen for serous and endometrioid type ovarian cancer.
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PMID:[Chemotherapy of ovarian cancer with a combination of low-dose consecutive CDDP and cyclophosphamide]. 849 34

Carboxyamido-triazole (CAI) is a synthetic inhibitor of non-excitable calcium channels that reversibly inhibits angiogenesis, tumor cell proliferation, and metastatic potential. Inhibition of calcium influx and calcium-dependent events is a potential common mechanism underlying these effects of CAI. The cytostatic and antiangiogenic properties of CAI led to its development for clinical investigation. In a Phase I clinical trial open to patients with refractory solid tumors, 49 patients received p.o. administered CAI daily or every other day. Two oral formulations, PEG-400 CAI solution and a gelatin capsule containing CAI in PEG-400, were tested. All administered dosages of CAI yielded plasma concentration at or above the range demonstrated to be effective in inhibiting signaling and cancer progression in vitro and in preclinical models (1 microgram/ml, 2.3 microM). Toxicity of p.o. administered CAI most commonly consisted of dose-related grade 1-2 nausea, vomiting, and occasional anorexia. CAI administration at bedtime ameliorated gastrointestinal complaints in many patients; others required addition of simple antiemetic regimens, usually consisting of metoclopropamide or prochlorperazine. Gastrointestinal complaints were the cause for compliance-limiting toxicity at 175 mg/m2/day of the liquid formulation and 125 mg/m2/day of the gelatin capsule formation. Reversible and rare sensory axonal neuropathy (grade 3, 1 patient) and neutropenia (grade 4, 1 patient) were dose-limiting toxicities observed at the 330 mg/m2 every-other-day liquid CAI dose level. No evidence of cumulative end organ damage or central nervous system injury was observed. Disease stabilization and improvement in performance status was observed. Disease stabilization and improvement in performance status was observed in 49% of evaluable patients who had disease progression before CAI. Disease stabilization and associated improvement in performance status was seen in patients with renal cell carcinoma (7 months), pancreaticobiliary carcinomas (3, 5, and 5 months), melanoma (7 months), ovarian cancer (7 months), and non-small cell lung cancer (3 months). The recommended Phase II doses from this trial are 150 mg/m2/day in the liquid formation and 100 mg/m2/day in the gelatin capsule formation.
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PMID:Clinical investigation of a cytostatic calcium influx inhibitor in patients with refractory cancers. 856 73

A large study of tumors of low malignant potential confirmed the favorable survival in this group of patients compared to invasive epithelial ovarian tumors. Only 8% of patients died with recurrent disease after surgery. Patients with stage IA borderline tumors with mucinous histology tended to recur later and carried a poorer prognosis than patients with serous histology and similar stage. The group at highest risk for relapse were age greater than 70, stage II or III tumors, and histology other than serous. Long-term survival in this group was less than 75%. This high-risk group of patients should be targeted for innovative adjuvant treatment strategies. This year several well-designed studies with large sample sizes showed DNA ploidy to be an important new independent prognostic factor in stage I ovarian carcinoma. In patients with well-differentiated early stage ovarian cancer, DNA flow cytometric analysis may indicate subgroups with less favorable prognostic characteristics. This method of analysis may be beneficial in determining the need for additional treatments after surgery for early stage ovarian carcinoma. Recommendations for the definitive management of early stage ovarian cancer awaits completion of current GOG and European randomized prospective studies. Paclitaxel given in combination with platinum-containing agents is an intense area of research for treatment of advanced stage disease. Early data from a prospective randomized trial of patients with advanced ovarian cancer showed a higher response rate and longer disease-free survival in patients treated with paclitaxel and cisplatin compared to a standard regimen of cyclophosphamide and cisplatin. The impact of this treatment on long-term survival awaits maturation of data. Preliminary results evaluating G-CSF in combination with paclitaxel and cisplatin for dose escalation was reported. Paclitaxel, 250 mg/m2, and cisplatin, 75 mg/m2, were the maximally tolerated doses, with peripheral neuropathy or myalgias the dose limiting toxicities. Further studies are now underway to test the effect of dose-response with escalation therapies and to determine the optimal dose and schedule for the management of patients with advanced ovarian cancer. IL-3 significantly ameliorated neutropenia but did not prevent cumulative platelet toxicity in a regimen utilizing high-dose carboplatin. This mild improvement in myelosuppression was obtained at the cost of significant toxicity. Nausea, vomiting, malaise, bone pain, headache, fever, chills and facial flushing were frequent. Intraperitoneal chemotherapy was tested as a means of consolidation treatment for patients after having a negative second-look laparotomy. These treatments were shown to be feasible; however, prospective randomized trials will be necessary to determine a benefit over operative therapy alone. Several studies addressed to problem of residual disease after primary surgery and adjuvant chemotherapy. A large phase II study conducted by the GOG confirmed the activity of salvage cisplatin-based intraperitoneal chemotherapy in patients with small-volume residual ovarian cancer with favorable pretreatment characteristics. Whether intraperitoneal platinum-based therapy represents an advantage over systemic platinum therapy is being addressed in a prospective SWOG study. The use of six additional cycles of CAP for treatment of residual disease after primary treatment of surgery and adjuvant chemotherapy did not significantly improve complete pathological response and survival. Prolonged duration of chemotherapy above six cycles is not likely to impact treatment for residual disease. A regimen of high dose carboplatin was compared to whole abdominal radiotherapy for treatment of residual disease after initial chemotherapy. There was no difference in survival or disease-free survival between treatments.(ABSTRACT TRUNCATED)
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PMID:Gynecological malignancies. 863 1

Fifty-one patients with histologically confirmed epithelial stage III or IV ovarian cancer were entered into a study in which gemcitabine 800 mg/m2 was given as a 30 min intravenous infusion in a cycle once a week for 3 weeks followed by a week of rest. Patients were aged 58 years (range 23-70 years) with WHO performance status 0-2, and had received up to two different chemotherapy regimens. Thirty-eight patients had received only one prior platinum-containing chemotherapy regimen whereas 9 had received a first-line regimen on more than one occasion. A further 3 patients had received two different regimens. Of 42 patients evaluable for response, 8 (19%; 95% CI: 9%-34%) were partial responders. Seven of the 8 responders were resistant to first-line platinum-based therapy. Median duration of response was 8.1 months (range 4.4-12.5 months). Median progression-free survival was 2.8 months (range 0.2-12.5 months). Haematological toxicity with gemcitabine was modest, with grade 3 leukopenia (11 patients) and grades 3 and 4 thrombocytopenia (6 patients). Grade 3 non-haematological toxicity included nausea/vomiting (6 patients) and elevated AST/ALT (1 patient), while dose-limiting non-haematologic toxicity consisted of flu-like symptoms (2 patients), peripheral oedema (1 patient) and lethargy (1 patient). The activity and modest haematological and non-haematological toxicity seen with gemcitabine suggest that this agent should be further evaluated in the treatment of patients with ovarian cancer and in combination chemotherapy regimens, primarily in combination with platinum.
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PMID:Phase II study of gemcitabine in previously platinum-treated ovarian cancer patients. 871 27

We compared, in a multicentric randomised prospective study, the efficacy and toxicity of carboplatin 400 mg/m2 as a single agent (CB) to a combination of carboplatin 300 mg/m2, epirubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (CB-EC) in advanced ovarian cancer patients. The treatment was scheduled to be administered every 3 weeks for six courses. Following initial laparotomy and cytoreductive surgery, 130 previously untreated patients entered the study. 73 patients were treated with carboplatin alone while 57 received the combination chemotherapy. In the majority of the patients, the regimens had to be given every 4 weeks due to myelosuppression. Nausea, vomiting and alopecia were more severe in the CB-EC arm. Overall, clinical complete response was observed in 73 (56%) and partial response in 20 (15%) patients. The median time to progression was 16.89 months and median survival was 29.54 months. No significant differences in response rate, time to progression, disease-free survival and overall survival were observed between the two treatment arms. The prognostic role of residual disease after initial surgery, complete remission at second-look laparotomy, tumour stage and performance status was confirmed.
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PMID:Carboplatin alone compared with its combination with epirubicin and cyclophosphamide in untreated advanced epithelial ovarian cancer: a Hellenic co-operative oncology group study. 881 85

Side effects of cisplatin and carboplatin include nausea, vomiting, peripheral neuropathy, nephrotoxicity, hearing loss, bone marrow depression, and rarely Lhermitte's sign and allergic reactions. A unique case of idiosyncrasy related to carboplatin administration was observed in a young woman treated for ovarian cancer. Symptoms and signs included skin rash, shortness of breath, and redness of face and upper trunk, without drop in blood pressure or change in heart rate, and were resolved within a short time following administration of hydrocortisone and promethazine.
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PMID:Carboplatin-related idiosyncrasy. 884 91

We investigated how residual tumour burden after cytoreductive surgery was related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian cancer patients receiving their first chemotherapy course. The anti-emetic treatment included ondansetron combined with dexamethasone or placebo. After chemotherapy all patients received ondansetron only for 5 days. Two categories of tumour burden (TB) were formed according to the diameter of the greatest residual tumour (< 2 cm = minimal TB and > or = 2 cm = large TB). Self-reports of nausea and vomiting were obtained for 15 days. Other potential predictor variables were assessed and included in multivariate analyses. Patients with large compared with minimal TB had more delayed emesis, especially on days 2-7. They also had more acute nausea. The aggravating effect associated with large residual TB was more evident in patients > or = 55 years. During the second week after the chemotherapy the occurrence of nausea was higher in patients > or = 55 years than in those < 55 years. This was seen primarily in patients with large residual TB. Predictors for no delayed emesis at all were anti-emetic treatment with dexamethasone, minimal tumour burden, low neuroticism and no history of motion sickness. The increased risk of "persistent' delayed nausea and vomiting seen in older patients with large tumour burden may have important clinical implications and warrants further attention.
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PMID:Impact of tumour burden on chemotherapy-induced nausea and vomiting. 885 84

The antiemetic effect of ondansetron (a 5-HT3 antagonist) was evaluated in patients treated with intraperitoneally administered anti-neoplastic agents (cisplatin and mitomycin-C) during surgery for ovarian cancer. Anesthesia was induced with intravenous thiopental 5 mg x kg-1 and maintained with nitrous oxide 66% in oxygen and isoflurane. After surgery, 6 patients received a single intravenous dose of ondansetron 4 mg (group O), 6 others did not receive ondansetron (group C). Both groups received an intravenous dose of methyl-prednisolone 500 mg. An intravenous dose of metoclopramide 10 mg was provided in case of continued vomiting or at the patient's request as a rescue antiemetic. The incidence of vomiting was 13% in group O and 87% in group C (P < 0.05). Nausea scores (range 1-4) were significantly lower in group O as compared with group C at 4 h and 8 h after surgery. Total dose of metoclopramide was 20 +/- 13 mg (mean +/- SD) in group C and 2 +/- 4 mg in group O. Administration of anti-neoplastic agents during surgery caused severe nausea and vomiting after surgery and ondansetron prevented the occurrence of nausea and vomiting almost completely. We conclude that ondansetron is an effective antiemetic for preventing postoperative nausea and vomiting in patients administered anti-neoplastic agents.
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PMID:[Treatment of postoperative nausea and vomiting with ondansetron in patients administered anti-neoplastic agents]. 890 45


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